- How Rheumatoid Arthritis Affects the Lungs
- Interstitial Lung Disease
- The Signs Arthritis Is Affecting Your Lungs, and the 3 Things You Must Do to Protect Them
- What Exactly Does Arthritis Do to Your Lungs?
- How to Help Keep Your Lungs Healthy
- Keep Reading
- Annals of the American Thoracic Society
- A 73‐year‐old woman with rheumatoid arthritis and shortness of breath
- Back on the courts
- Lung Disease Frequently Fatal in Rheumatoid Arthritis
- Differential diagnosis
- Methotrexate-associated lung disease in rheumatoid arthritis
How Rheumatoid Arthritis Affects the Lungs
Despite its name, rheumatoid arthritis (RA) doesn’t just affect your joints. It can also damage the tissue surrounding the joints, as well as your eyes, heart, and lungs.
“We call it rheumatoid arthritis, but we should really call it rheumatoid disease,” says Elinor Mody, MD, assistant professor at Harvard Medical School and director of the Women’s Orthopedic and Joint Disease Program at Brigham and Women’s Hospital in Boston.
Rheumatoid arthritis can damage the whole body. Besides the joints, the “heart and lungs are the most commonly affected,” Dr. Mody says. Doctors aren’t sure how or why rheumatoid arthritis causes other organs to suffer, but lung complications from RA can be serious and even cause death.
Interstitial Lung Disease
Rheumatoid arthritis–associated interstitial lung disease, or RA-ILD, is one of the most serious lung complications for people with rheumatoid arthritis. This illness can be hard to detect, but occurs when lung tissue becomes inflamed and eventually scarred. Here’s what we do know:
- Risk Factors Men are at higher risk than women for this disease. Although nonsmokers can and do develop RA-ILD, smoking seems to increase risk.
- Symptoms RA-ILD may cause breathlessness and dry cough, but in many cases it causes no symptoms at all, making early detection difficult.
- Treatment More research is still needed to find effective treatment. “This is a difficult disease to treat,” Mody says. According to a review published in March 2015 in the journal European Respiratory Review, recent studies have looked at the drug Rituxan (rituximab) for the treatment of RA-ILD, but the results have been conflicting and it’s not clear whether it improves or worsens the condition. Some other drugs, like azathioprine (Azasan, Imuran), cyclosporine (Gengraf, Neoral), and cyclophosphamide (Cytoxan), are used to treat RA-ILD.
The Signs Arthritis Is Affecting Your Lungs, and the 3 Things You Must Do to Protect Them
We say “rheumatoid arthritis,” you think joints — which, of course, makes sense. Rheumatoid and other forms of inflammatory arthritis are notorious for causing pain, stiffness, and swelling in your hands, feet, lower back, and other joints.
But the same chronic, systemic inflammation that targets those joints can also affect other seemingly unrelated parts of your body — such as your heart and your lungs. (Here’s how to protect your heart when you live with inflammatory arthritis.)
Some reports suggest about 10 to 20 percent of patients with rheumatoid arthritis have lung problems. One study published in the journal Rheumatology International found that number may be as high as 67 percent. Most cases of lung disease will occur within five years of being diagnosed.
What Exactly Does Arthritis Do to Your Lungs?
Inflammation from arthritis may damage the tissue, inflame the lining, or raise your risk of lung disease. Some lung problems linked to inflammatory arthritis include:
Scarring within the lungs
In medical speak, it’s called interstitial lung disease (ILD) — a broad category of lung disorders, most of which lead to scarring (fibrosis) in the tissue between the air sacs of the lungs (called the interstitium). Chronic inflammation from rheumatoid arthritis can lead to this scarring; over time, the buildup of scar tissue makes the lung tissue stiff, which interferes with breathing and can be difficult to treat.
ILD is the most common and most serious lung complication for people with RA: Research shows lung disease alone accounts for up to 20 percent of deaths in rheumatoid arthritis patients, and most are attributed to ILD. Though it’s rare, this scarring may also occur in a small number of people with ankylosing spondylitis.
Symptoms include shortness of breath and dry cough, as well as fatigue and weight loss. But by the time these signs appear, irreversible lung damage has often already occurred. Some estimates suggest about 30 percent of patients with rheumatoid arthritis have ILD, without obvious symptoms.
Nodules from Rheumatoid Arthritis in Lungs
These firm bumps of tissue, or rheumatoid nodules, might form in the lungs. They don’t typically cause symptoms, nor do they pose a risk for lung cancer. Nodules range in size from a millimeter to centimeters in size, there may be one or a bunch, and they may come and go over time. In some cases, however, a nodule can rupture and caused a collapsed lung.
There are thin membranes that surround the lungs and line the inside of the chest cavity called the pleura. If that tissue becomes inflamed, it can cause discomfort in your chest. Fluid can also build up between the two layers — a condition called pleural effusion. The fluid may resolve on its own in some cases; a large amount of fluid, however, can lead to persistent coughing, shortness of breath, or a collapsed lung.
Chronic obstructive pulmonary disease (COPD)
Research published in the journal Arthritis Care & Research suggests people with RA are nearly twice as likely to be hospitalized for chronic obstructive pulmonary disease (COPD) than the general population. COPD is a chronic inflammatory lung disease that obstructs airflow to the lungs. Researchers note that many of the same markers of inflammation found in rheumatoid arthritis are elevated in COPD.
Increased Risk of Pneumonia
If you have rheumatoid, psoriatic, and other forms of inflammatory arthritis, you may have twice the normal risk for getting an infection like flu or pneumonia. That’s because these diseases decrease your body’s natural immune defenses, and therefore increase your risk of serious infection. Plus, certain medications you take to manage your condition also weaken or suppress the immune response, leaving you that much more susceptible.
Less lung capacity
Ankylosing spondylitis causes some of the vertebrae in your spine to fuse, which makes your spine less flexible. In severe cases, this fusion can also stiffen your rib cage, restricting your lung capacity and making it more difficult to breathe deeply.
How to Help Keep Your Lungs Healthy
After heart disease, lung disease is the second-most common cause of death in rheumatoid arthritis. To help protect your lungs follow these three steps:
1. Quit smoking. It’s harmful to your health in a million different ways. And the chemicals in cigarettes can irritate lung tissue even more. To get help, talk to your doctor or go to smokefree.gov. Quitting smoking can also help you achieve remission for your arthritis.
2. Get vaccinated. Respiratory infections are common infections in RA, and complications could be severe. There are two types of pneumonia vaccines — talk to your doctor about which ones you need and when you should get them. The annual flu shot is another must. Here’s what you need to know about getting the flu vaccine when you have arthritis.
3. Report any breathing problems to your doctor. Regular check-ups are important so your doctor can monitor your lungs. But be sure to tell your physician right away if you experience shortness of breath, consistent coughing, or other respiratory symptoms. Lung issues that are detected earlier may be easier to treat.
- 7 Tips You Need to Beat Arthritis Fatigue
- Arthritis Gloves: Do They Actually Relieve Swelling and Pain?
- The 4 Stages of Rheumatoid Arthritis Progression
Annals of the American Thoracic Society
Leflunomide is a disease-modifying antirheumatic drug (DMARD) that has been available in the United States since 1998. Leflunomide is converted by first-pass metabolism in the lining of the gut and hepatocytes to the active compound teriflunomide. The mechanism of action of teriflunomide is somewhat unique as a DMARD. Teriflunomide inhibits dihydrooroatase dehydrogenase, thereby preventing the activation of T lymphocytes. Teriflunomide undergoes significant enterohepatic circulation, leading to a prolonged half-life of approximately 15 to 18 days. When serious hepatic or pulmonary complications are suspected, interruption of this cycling with administration of either oral cholestyramine or activated charcoal will rapidly reduce the serum concentrations of teriflunomide (2, 7).
Initial clinical trials showed leflunomide had a safety and efficacy profile similar to that of methotrexate and other DMARDs (2). The most common adverse events for leflunomide administration include gastrointestinal symptoms, transaminase elevations, allergic reactions, alopecia, neutropenia, rash, and hypertension (9). During initial clinical trials and subsequent early postmarket surveillance, there were no reports of interstitial lung disease associated with leflunomide. However, in 2004 case reports describing an association of leflunomide with interstitial lung disease (LEF-ILD) appeared. The incidence of LEF-ILD was reported to be 0.5% in the Japanese populations studied. With the added concern for lung toxicity, studies were undertaken to delineate the incidence and risk factors for development of LEF-ILD. Investigations indicated that the incidence in Western countries was 0.08% (3). Subsequent analysis suggests that channeling bias may explain some of the differences in prominence of the interstitial lung disease seen between Western and Far East countries (2). Of note, the pathology of LEF-ILD can be variable, and different reports have described interstitial pneumonitis with variable eosinophilia, organizing pneumonia, or diffuse alveolar damage (3).
With the growing use of leflunomide in clinical practice, early recognition and appropriate therapy of LEF-ILD is increasingly important. Leflunomide is being used to treat an expanding scope of conditions, including: RA, sarcoidosis, psoriasis, systemic lupus erythematosus, atopic dermatitis, Sjögren’s disease, minimal change disease, solid organ transplantation, relapsing forms of multiple sclerosis, and a growing list of other disorders (6). In addition to expanded use as monotherapy, leflunomide is being used in combination with other DMARDs. Recent data were not able to establish an increased risk of LEF-ILD in combination therapy but may have been underpowered to detect this difference (8). There is also research that suggests genetic polymorphisms may dictate higher doses of leflunomide be administered in some patients to achieve adequate serum teriflunomide levels (9). Continued diligence in postmarketing analysis will be required to determine if higher doses or use in combination therapy is associated with increased frequency of LEF-ILD, as administration of a loading dose has been associated with increased risk of interstitial lung disease (4, 8).
Leflunomide-induced lung disease is associated with a mortality rate of 19% (3). In an attempt to understand the risk factors that contribute to the development of LEF-ILD, review of extensive postmarketing data revealed risk factors for LEF-ILD included: previous diagnosis of interstitial lung disease (odds ratio , 8.168), history of smoking (OR, 3.115), use of a loading dose with initiation of therapy (OR, 3.996), and body weight less than 40 kg (OR, 2.909) (4). Increased mortality is seen in patients who presented with the following: hypoxemia (defined as a PaO2 < 60 mm Hg or oxygen saturation < 90%), elevated serum C-reactive protein, CT evidence of diffuse alveolar damage, and lower serum albumin (5).
A 73‐year‐old woman with rheumatoid arthritis and shortness of breath
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Dr. Aryeh Fischer.
RA is very common. It affects about 1 percent of the population worldwide. Few people know that RA also commonly involves organs, not just joints. And the lungs are a favorite target. Clinicians and researchers are gaining a much better understanding of how RA affects patients throughout their bodies thanks to significantly improved imaging technology.
“It’s a systematic inflammatory disease that likes the joints,” Fischer said. “But, it’s not just a joint disease. It’s a disease of the immune system that can affect multiple systems in the body. For example, RA may involve the eyes, lungs and the heart.”
Because much of the morbidity of systemic autoimmune disease involves the lungs, Dr. Fischer considers himself “a lung-obsessed rheumatologist.”
Patients see him for RA and he wants them to also undergo a chest CT scan.
“We’re learning that there aren’t hard and fast rules about this disease,” Fischer said. “The textbooks say that patients are supposed to have really bad joint disease, then you get lung disease. In real life, some people start with lung disease years before they develop arthritis. We need to break down our simplistic versions of these diseases.”
A multi-disciplinary approach is essential for patients like Hutchison.
“Can you imagine seeing a rheumatologist for 20 years and suddenly you have lung involvement and now, you’re supposed to leave that doctor and go find a lung doctor? We have silos in medicine and patients end up having to go back and forth across town to see different doctors for the same problem. And sometimes the doctors are pointing fingers at each other,” Fischer said.
Dr. Joyce Lee.
UCHealth’s University of Colorado Hospital recruited both Fischer and Lee in recent years from top programs around the country. Now Colorado patients coping with RA and ILD can find the help they need in one place.
While there’s no cure for RA associated ILD, Lee said researchers are continuing to make progress.
“The horizon is bright. We’re not quite there, but it’s encouraging that there are a lot more investigators here and around the world who are working on this,” she said.
Lee and Fischer keep a close eye on Hutchison with frequent monitoring and lung function tests.
“He’s doing great,” Fischer said.
When the RA flares, Hutchison does infusions of a drug called rituximab. There aren’t as many good medicines for his lung condition, but Lee and Fischer said they expect therapies to keep improving.
“We’ve all got to keep working on this together from clinical care to research”, Fischer said.
Back on the courts
Along with ideal therapies, the causes for RA and ILD remain elusive.
Genetics may play a big role. But there are other risk factors.
Unfortunately, Hutchison has one that he wishes he could erase.
“I was a big smoker,” he said. “I’d give anything to go back and not have smoked.”
Hutchison is so athletic that it seems impossible that he was once a big smoker. Back in high school, he was the MVP his senior year for the high school tennis team.
But he and Mary Anna grew up in tobacco country.
“My uncles grew tobacco. Her mom worked at Phillip Morris,” Hutchison said.
Cigarettes were central to the community, the culture and the economy. When Mary Anna’s mom wrote checks, she proudly added a stamp to each saying, “This is tobacco money.”
She brought home endless samples of Marlboros and Virginia Slims.
Hutchison thinks he started smoking at age 9 or 10. He cringes at the memory of playing basketball with a Pall Mall hanging out of his mouth.
“I loved smoking, but I knew it killed you,” he said.
Sonnyand Mary Anna Hutchison used to have birds as pets. For some people, allergies to birds can cause lung troubles. Photo courtesy of Sonny Hutchison.
The addiction was potent.
“I tried and tried to quit. It’s brutal,” he said. “I finally quit for good in around ’87.”
In addition to the smoking being a risk, a doctor several years ago theorized that an allergy to birds could be aggravating Hutchison’s lungs.
The Hutchisons had a green and blue cockatiel with orange cheeks and a pale blue parakeet.
“We loved them. They were a pain, but they were beautiful,” Hutchison said.
Nonetheless, they got rid of the birds.
Dr. Lee said exposure to birds can cause lung problems, but she doesn’t think they were the source of Hutchison’s fibrosis.
“The main thing we’re looking into now is the role of genetics and other risk factors, including the smoking link,” Lee said.
Hutchison is grateful to have his doctors in his corner.
“They’re both brilliant,” he said.
Hutchison’s lung function tests continue to be good enough that he hasn’t needed supplemental oxygen. He works out regularly and, with his partner, is doing a film for the National Park Service on native Hawaiians.
And the tennis is going great. His team is doing well. This year, Hutchison traveled to Texas to do a weeklong camp at Australian pro John Newcomb’s tennis ranch, where he played for hours a day.
His men’s team did well again. He and his doubles partner won the club championship in their division.
And most rewarding of all are the matches he and his friends play for fun. The victors get fake trophies that the men make. (Yes, glue guns are involved and the “trophies” look like Kindergarten art projects.)
There’s plenty of trash talking and laughing during the matches. And afterwards, the men sometimes indulge in another prize.
“Occasionally, there might be a little bourbon involved,” Hutchison confides with a big grin.
And, of course, it’s from Kentucky.
Lung Disease Frequently Fatal in Rheumatoid Arthritis
The likelihood of dying is significantly increased in patients with rheumatoid arthritis who have interstitial lung disease compared with patients who do not.
Mortality is particularly high during the first month after a combined diagnosis of rheumatoid arthritis complicated by interstitial lung disease.
Diagnostic delay may prove fatal, especially if the interstitial lung disease is already severe at presentation.
New treatments for patients with rheumatoid arthritis have caused the mortality rate to decline over the past 10 years. But even with improvements in mortality, the risk of death in patients with rheumatoid arthritis is still higher than in the general population. Most of the deaths are related to cardiovascular disease and interstitial lung disease.
Although interstitial lung abnormalities may be detected in as many as half of patients with rheumatoid arthritis before they are clinically evident, Charlotte Hyldgaard and colleagues from Denmark pointed out that the risk of progressing to clinically significant lung disease is unknown.
The authors compared mortality rates among patients who have rheumatoid arthritis and interstitial lung disease and those who have rheumatoid arthritis alone. They presented their findings in a recent Annals of the Rheumatic Diseases article.
They conducted a population cohort study that included 31,333 patients with rheumatoid arthritis. The incidence of comorbid interstitial lung disease and mortality was examined.
• Of the patients in the cohort with rheumatoid arthritis, 2.2% had interstitial lung disease.
• Patients with rheumatoid arthritis who had interstitial lung disease were more likely to be older men with seropositivity.
• A diagnosis of interstitial lung disease before rheumatoid arthritis was made in 14% of cases.
• In 34% of cases, a diagnosis of interstitial lung disease was made within 1 year of, at the same time as, or within the first year after rheumatoid arthritis diagnosis.
• Comorbidities were seen more frequently in the interstitial lung disease group. They included ischemic heart disease, congestive heart failure, and diabetes.
See also separate Rheumatoid Arthritis article.
Lung disease is a well-recognised and important extra-articular manifestation of rheumatoid arthritis. A study in New Zealand of patients recently diagnosed with rheumatoid arthritis found that 30% of patients reported respiratory symptoms (dyspnoea, cough, wheeze), 20% of patients had physiological evidence of airflow obstruction and 40% had reduced gas transfer. The prevalence of abnormalities found with high-resolution CT was decreased attenuation in 67%, bronchiectasis in 35%, bronchial wall thickening in 50%, ground glass opacification in 18% and reticular changes in 12% of patients.
The range of pulmonary problems associated with rheumatoid arthritis includes:
- Rheumatoid nodules:
- The only pulmonary manifestation specific to rheumatoid arthritis.
- They are typically benign but can lead to pleural effusion, pneumothorax, haemoptysis, secondary infection, and bronchopulmonary fistula.
- Caplan’s syndrome:
- See also separate Caplan’s Syndrome article.
- In 1953, Caplan described a characteristic radiographic pattern in coal miners with rheumatoid arthritis that was distinct from the typical progressive massive fibrosis pattern of coalworkers’ pneumoconiosis.
- CXRs show multiple well-defined rounded nodules, which are about 0.5-2 cm in diameter, distributed throughout the lungs but predominantly at the lung periphery.
- Interstitial lung disease (ILD):
- ILD and airways disease are the most common forms of rheumatoid arthritis-related lung disease.
- ILD can be present in most types of connective tissue disease, including rheumatoid arthritis, scleroderma, systemic lupus erythematosus, polymyositis or dermatomyositis, Sjögren’s syndrome and mixed connective tissue disease.
- ILD most often occurs in middle-aged men. It is usually associated with severe arthritis and high serum levels of rheumatoid factor.
- It presents with insidious onset of dyspneoa with occasional dry cough.
- Associated pulmonary vasculitis may cause pulmonary hypertension.
- Bronchiolitis obliterans with organising pneumonia: clinical features include cough, shortness of breath, and bilateral crackles. The vital capacity is slightly decreased and the diffusing capacity is moderately to severely decreased. High-resolution chest CT scan shows bilateral ground-glass opacities with air bronchograms and triangular, pleura-based opacities. Steroids are the best treatment option. The prognosis is generally good, with resolution and cure for most patients.
- Obliterative bronchiolitis: a rare, usually fatal condition. Associated with penicillamine, gold, and sulfasalazine treatment. Presents with rapid-onset dyspnoea and dry cough. Fever is uncommon.
- See also separate Bronchiectasis article.
- Bronchiectasis co-existing with rheumatoid arthritis differs from the other types of bronchiectasis.
- Patients with rheumatoid arthritis and bronchiectasis have worse obstructive airways disease, increased susceptibility to recurrent lower respiratory tract infections, faster lung function decline and higher mortality compared with subjects with bronchiectasis alone.
- Arteritis of the pulmonary artery and lung is rare; signs of systemic vasculitis are usually present.
- Respiratory infections account for 15-20% of deaths in rheumatoid patients.
- Drug toxicity:
- Acute interstitial pneumonitis may occur in 1-5% of patients treated with methotrexate (see ‘Methotrexate-associated lung disease in rheumatoid arthritis’, below).
- Penicillamine and gold may also cause pulmonary complications.
- Pleural effusions:
- See separate Pleural Effusion article.
- Pleural effusions in rheumatoid arthritis are usually small, unilateral and asymptomatic.
- Occasionally, an empyema may develop
- Lung cancer: is more common in patients with rheumatoid arthritis than in normal control subjects.
- Other diseases:
- Rheumatoid arthritis patients can get apical fibro-bullous disease (apical fibrotic cavity lesions similar to ankylosing spondylitis).
- Thoracic cage immobility causing restrictive lung disease.
- Primary pulmonary hypertension (rare); secondary pulmonary hypertension (due to ILD) is more common.
Rheumatoid arthritis is often associated with pleural disease (20-40%), interstitial pneumonitis (5-10%), nodules (1%), interstitial fibrosis, bronchiolitis obliterans organising pneumonia, and pulmonary vasculitis.
The association of rheumatoid arthritis with lung disease may be due to:
- Rheumatoid-associated lung disease.
- Drug-related lung disease secondary to drugs used to treat rheumatoid arthritis.
- Infection secondary to immunosuppression.
- Co-existent medical conditions – eg, chronic obstructive pulmonary disease.
- Blood tests for evaluation of rheumatoid arthritis, including serology.
- Respiratory function tests, including spirometry.
- Aspiration of pleural fluid.
- CT or MRI scan.
- Lung biopsy.
There are several management guidelines, including those from the National Institute for Health and Care Excellence (NICE). These are important guidelines for improvement of the management of rheumatoid arthritis. They do not include details of the management of lung disease in rheumatoid arthritis.
ILD caused by rheumatoid arthritis is usually treated with a corticosteroid or a combination of a corticosteroid and azathioprine or cyclophosphamide. Methotrexate is also being increasingly used.
- ILD associated with rheumatoid arthritis causes significant morbidity and mortality.
- Mortality is high in patients who develop ILD and pulmonary hypertension.
- The median survival of all patients with ILD associated with rheumatoid arthritis has been reported to be approximately five years.
Methotrexate-associated lung disease in rheumatoid arthritis
- Methotrexate pneumonitis is an unpredictable and life-threatening side-effect of methotrexate therapy.
- Presentation is often subacute with symptoms often present for several weeks or months before diagnosis.
- It presents most often with cough, dyspnoea and fever. It may progress rapidly to respiratory failure.
- Early diagnosis, cessation of methotrexate, and treatment with corticosteroids and/or cyclophosphamide are important in management.
- There is a high rate of recurrence of lung injury after re-challenge with methotrexate.